Allosteric Modulation of αβδ GABA_A Receptors

Publisher： MDPI

E-ISSN： 1424-8247|3|11|3461-3477

ISSN： 1424-8247

Source： Pharmaceuticals, Vol.3, Iss.11, 2010-11, pp. : 3461-3477

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Abstract

GABA_A receptors mediate the majority of the fast inhibition in the mature brain and play an important role in the pathogenesis of many neurological and psychiatric disorders. The αβδ GABA_A receptor localizes extra- or perisynaptically and mediates GABAergic tonic inhibition. Compared with synaptically localized αβγ receptors, αβδ receptors are more sensitive to GABA, display relatively slower desensitization and exhibit lower efficacy to GABA agonism. Interestingly, αβδ receptors can be positively modulated by a variety of structurally different compounds, even at saturating GABA concentrations. This review focuses on allosteric modulation of recombinant αβδ receptor currents and αβδ receptor-mediated tonic currents by anesthetics and ethanol. The possible mechanisms for the positive modulation of αβδ receptors by these compounds will also be discussed.